The Impact of Left Atrium Appendage Morphology on Stroke Risk Assessment in Atrial Fibrillation: A Computational Fluid Dynamics Study.

Atrial fibrillation (AF) carries out a 5-fold increase in stroke risk, related to embolization of thrombi clotting in left atrium (LA). Left atrial appendage (LAA) is the site with the highest blood stasis which causes thrombus formation. About 90 % of the intracardiac thrombi in patients with cardioembolic events originally develop in the LAA. Recent studies have been focused on the association between LAA anatomical features and stroke risk and provided conflicting results. Haemodynamic and fluid dynamic information on the LA and mostly on the LAA may improve stroke risk stratification. Therefore, the aim of this study was the design and development of a workflow to quantitatively define the influence of the LAA morphology on LA hemodynamics. Five 3D LA anatomical models, obtained from real clinical data, which were clearly different as regard to LAA morphology were used. For each LAA we identified and computed several parameters describing its geometry. Then, one LA chamber model was chosen and a framework was developed to connect the different LAAs belonging to the other four patients to this model. These new anatomical models represented the computational domain for the computational fluid dynamics (CFD) study; simulations of the hemodynamics within the LA and LAA were performed in order to evaluate the interplay of the LAA shape on the blood flow characteristics in AF condition. CFD simulations were carried out for five cardiac cycles. Blood velocity, vorticity, LAA orifice velocity, residence time computed in the five models were compared and correlated with LAA morphologies. Results showed that not only complex morphologies were characterized by low velocities, low vorticity and consequently could carry a higher thrombogenic risk; even qualitatively simple morphologies showed a thrombogenic risk equal, or even higher, than more complex auricles. CFD results supported the hypothesis that LAA geometric characteristics plays a key-role in defining thromboembolic risk. LAA geometric parameters could be considered, coupled with the morphological characteristics, for a comprehensive evaluation of the regional blood stasis. The proposed procedure might address the development of a tool for patient-specific stroke risk assessment and preventive treatment in AF patients, relying on morpho-functional defintion of each LAA type.

Comparison of Total Kidney Volume Quantification Methods in Autosomal Dominant Polycystic Disease for a Comprehensive Disease Assessment.

BACKGROUND: In recent times, the scientific community has been showing increasing interest in the treatments aimed at slowing the progression of the autosomal dominant polycystic kidney disease (ADPKD). Therefore, in this paper, we test and evaluate the performance of several available methods for total kidney volume (TKV) computation in ADPKD patients - from echography to MRI - in order to optimize patient classification. METHODS: Two methods based on geometric assumptions (mid-slice [MS], ellipsoid [EL]) and a third one on true contour detection were tested on 40 ADPKD patients at different disease stage using MRI. The EL method was also tested using ultrasound images in a subset of 14 patients. Their performance was compared against TKVs derived from reference manual segmentation of MR images. Patient clinical classification was also performed based on computed volumes. RESULTS: Kidney volumes derived from echography significantly underestimated reference volumes. Geometric-based methods applied to MR images had similar acceptable results. The highly automated method showed better performance. Volume assessment was accurate and reproducible. Importantly, classification resulted in 79, 13, 10, and 2.5% of misclassification using kidney volumes obtained from echo and MRI applying the EL, the MS and the highly automated method respectively. CONCLUSION: Considering the fact that the image-based technique is the only approach providing a 3D patient-specific kidney model and allowing further analysis including cyst volume computation and monitoring disease progression, we suggest that geometric assumption (e.g., EL method) should be avoided. The contour-detection approach should be used for a reproducible and precise morphologic classification of the renal volume of ADPKD patients.

Geometry-independent assessment of renal volume in polycystic kidney disease from magnetic resonance imaging.

Total renal volume (TRV) is an important quantitative indicator of the progression of autosomal dominant polycystic kidney disease (ADPKD). The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease proposes a method for TRV computation based on manual tracing and geometric modeling. We developed a fast and nearly-automated technique for kidney segmentation and automatically compute TRV. In this study we aim to compare TRV estimates derived from these two different approaches. The highly-automated technique for the analysis of MR images was tested on 30 ADPKD patients. TRV was computed from both axial and coronal acquisitions, and compared to measurements based on geometric modeling by linear regression and Bland Altman analysis. In addition, to assess reproducibility, intra-observer and inter-observer variabilities were computed. The results of this study provide the feasibility of using a nearly-automated approach for accurate and fast evaluation of TRV also in markedly enlarged ADPKD kidneys.

3D dynamic position assessment of the coronary sinus lead in cardiac resynchronization therapy.

Although cardiac resynchronization therapy (CRT) is an effective treatment for chronic systolic heart failure with dyssynchrony, about one-third of patients do not respond favorably. The interaction between the pacing lead and the coronary sinus (CS) branches is of paramount importance for an effective resynchronization. Minor changes in lead position overtime could interfere with CRT mechanics, without affecting even biophysical parameters or ECG morphology. Although late post-implant CS lead dislodgement rate is consistent, lead movements have been little investigated and only with bi-dimensional methods. The aim of this study was (1) to develop a method for quantifying CS lead position in the 3D domain throughout the cardiac cycle and (2) to test it by comparing the CS lead position at implant and at follow-up, using chest fluoroscopy. Method performance, its accuracy and reproducibility were qualitatively and quantitatively assessed. Intra- and inter-observer percent discordance between trajectories were also computed. The accuracy of the procedure resulted in 0.3 ± 0.1 mm and its resolution was 0.5 mm. Intra- and inter-observer discordances were 2.2 ± 1.5 and 5.5 ± 3.6 mm, respectively. The proposed method for measuring the CS lead dynamic placement in 3D space seems accurate and reproducible. Investigating CS lead 3D dynamics could provide further insights into CRT mechanics.

Assessment of kidney volume in polycystic kidney disease using magnetic resonance imaging without contrast medium.

BACKGROUND/AIMS: Total renal volume (TRV) is an important index to evaluate the progression of autosomal-dominant polycystic kidney disease (ADPKD). TRV has been assessed by manually tracing renal contours from CT or MR scans, often employing contrast medium (CM). We developed a fast and nearly automated technique based on the analysis of MR images acquired without CM injection for TRV quantification. METHODS: 30 ADPKD patients underwent MRI. After the selection of one point inside each kidney for the entire volume, the automatic extraction of kidney contours was performed on each acquired slice; the segmentation procedure was based on region growing and on the application of morphological operators and curvature-based motion. The area inside each contour was calculated and TRV was derived. Volume measurements were validated by comparison with measurements obtained by stereology. RESULTS: TRV estimated in patients was 768 ± 545 ml (range 161-3,111 ml). The automatic measurements were in excellent correlation with the manual ones (r = 0.99, y = x - 0.7), with a small bias and narrow limits of agreement in both absolute (-5 ± 37 ml) and percentage (-0.6 ± 9.6%) terms. CONCLUSION: This preliminary study showed the feasibility of a fast and nearly automated method for determining TRV; importantly it does not require the use of potentially nephrotoxic CM.

Mechanisms of beta-adrenergic modulation of I(Ks) in the guinea-pig ventricle: insights from experimental and model-based analysis.

Detailed understanding of I(Ks) gating complexity may provide clues regarding the mechanisms of repolarization instability and the resulting arrhythmias. We developed and tested a kinetic model to interpret physiologically relevant I(Ks) properties, including pause-dependence and modulation by beta-adrenergic receptors (beta-AR). I(Ks) gating was evaluated in guinea-pig ventricular myocytes at 36 degrees C in control and during beta-AR stimulation (0.1 micromol/L isoprenaline (ISO)). We tested voltage dependence of steady-state conductance (Gss), voltage dependence of activation and deactivation time constants (tau(act), tau(deact)), and pause-dependence of tau(act) during repetitive activations (tau(react)). The I(Ks) model was developed from the Silva and Rudy formulation. Parameters were optimized on control and ISO experimental data, respectively. ISO strongly increased Gss and its voltage dependence, changed the voltage dependence of tau(act) and tau(deact), and modified the pause-dependence of tau(react). A single set of model parameters reproduced all experimental data in control. Modification of only three transition rates led to a second set of parameters suitable to fit all ISO data. Channel unitary conductance and density were unchanged in the model, thus implying increased open probability as the mechanism of ISO-induced Gss enhancement. The new I(Ks) model was applied to analyze ISO effect on repolarization rate-dependence. I(Ks) kinetics and its beta-AR modulation were entirely reproduced by a single Markov chain of transitions (for each channel monomer). Model-based analysis suggests that complete opening of I(Ks) channels within a physiological range of potentials requires concomitant beta-AR stimulation. Transient redistribution of state occupancy, in addition to direct modulation of transition rates, may underlie beta-AR modulation of I(Ks) time dependence.

Automated frame-by-frame endocardial border detection from cardiac magnetic resonance images for quantitative assessment of left ventricular function: validation and clinical feasibility.

PURPOSE: To develop a technique based on image noise distribution for automated endocardial border detection from cardiac magnetic resonance (CMR) images throughout the cardiac cycle, validate it, and test its clinical utility. MATERIALS AND METHODS: Images obtained in 36 patients were analyzed using custom software to obtain left ventricular (LV) volume throughout the cardiac cycle, end-systolic and end-diastolic LV volumes, and ejection fraction (EF). Validation against manually-traced endocardial boundaries included intertechnique comparisons of LV volumes, slice areas, and border positions. Then, the clinical feasibility of the dynamic automated analysis of LV function was tested in 14 patients with normal LV function, 12 patients with systolic dysfunction, and 10 patients with diastolic dysfunction. RESULTS: Analysis time for one cardiac cycle was <15 minutes. Intertechnique comparisons resulted in high correlation (r>0.96), small biases (volumes: -6 mL; EF: 4.6%) and narrow limits of agreement (volumes: 17.6 mL; EF: 9.2%). We found significant intergroup differences in multiple quantitative indices of systolic and diastolic function. CONCLUSION: Fast, automated, dynamic detection of LV endocardial boundaries is feasible and allows accurate quantification of LV size and function, which is potentially clinically useful for objective assessment of systolic and diastolic dysfunction.